CN113277959B - Synthesis method of ortho-perfluoroalkyl substituted azide compound - Google Patents

Synthesis method of ortho-perfluoroalkyl substituted azide compound Download PDF

Info

Publication number
CN113277959B
CN113277959B CN202011508287.0A CN202011508287A CN113277959B CN 113277959 B CN113277959 B CN 113277959B CN 202011508287 A CN202011508287 A CN 202011508287A CN 113277959 B CN113277959 B CN 113277959B
Authority
CN
China
Prior art keywords
cdcl
nmr
azido
radical initiator
alkyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202011508287.0A
Other languages
Chinese (zh)
Other versions
CN113277959A (en
Inventor
刘文博
黄宏贵
李维双
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Wuhan University WHU
Original Assignee
Wuhan University WHU
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Wuhan University WHU filed Critical Wuhan University WHU
Priority to CN202011508287.0A priority Critical patent/CN113277959B/en
Publication of CN113277959A publication Critical patent/CN113277959A/en
Application granted granted Critical
Publication of CN113277959B publication Critical patent/CN113277959B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C245/00—Compounds containing chains of at least two nitrogen atoms with at least one nitrogen-to-nitrogen multiple bond
    • C07C245/20—Diazonium compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C269/06—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/26—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids
    • C07C303/30—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids by reactions not involving the formation of esterified sulfo groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
    • C07C303/40—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reactions not involving the formation of sulfonamide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
    • C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C07D213/80—Acids; Esters in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C07D213/803—Processes of preparation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
    • C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
    • C07D275/04—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D275/06—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems with hetero atoms directly attached to the ring sulfur atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D307/62—Three oxygen atoms, e.g. ascorbic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
    • C07F7/1804—Compounds having Si-O-C linkages
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
    • C07F7/1804—Compounds having Si-O-C linkages
    • C07F7/1872—Preparation; Treatments not provided for in C07F7/20
    • C07F7/1892—Preparation; Treatments not provided for in C07F7/20 by reactions not provided for in C07F7/1876 - C07F7/1888
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/06—Phosphorus compounds without P—C bonds
    • C07F9/08—Esters of oxyacids of phosphorus
    • C07F9/09—Esters of phosphoric acids
    • C07F9/091—Esters of phosphoric acids with hydroxyalkyl compounds with further substituents on alkyl
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
    • C07J9/005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/36—Systems containing two condensed rings the rings having more than two atoms in common
    • C07C2602/42—Systems containing two condensed rings the rings having more than two atoms in common the bicyclo ring system containing seven carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/56—Ring systems containing bridged rings
    • C07C2603/58—Ring systems containing bridged rings containing three rings
    • C07C2603/70—Ring systems containing bridged rings containing three rings containing only six-membered rings
    • C07C2603/74—Adamantanes

Abstract

The invention discloses a synthesis method of an ortho-perfluoroalkyl substituted azide compound, which comprises the following steps: radical initiator, N 3 SO 2 C n F 2n+1 Adding the ortho perfluoroalkyl group substituted azide compound II and the alkene I into a solvent, stirring, and separating and purifying after reaction to obtain an ortho perfluoroalkyl group substituted azide compound II; wherein the free radical initiator is a peroxy compound or azo free radical initiator; the structure of the olefin I is
Figure DDA0002845562440000011
Wherein R is 1 、R 2 、R 3 、R 4 Each independently, optionally selected from hydrogen, alkyl, aryl-substituted alkyl, heteroatom-substituted alkyl, or halogen-substituted alkyl. Use of the invention N 3 SO 2 C n F 2n+1 The compounds act as perfluoroalkyl and azide precursors. The method has the advantages of simple and safe operation, easily obtained raw materials, mild reaction conditions, high atom economic efficiency and high reaction activity. The invention avoids using transition metal catalyst, not only has low economic cost, but also can effectively reduce heavy metal residue and the pollution of the reaction itself to the environment.

Description

Synthesis method of ortho-perfluoroalkyl substituted azide compound
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of an ortho perfluoroalkyl substituted azide compound.
Background
Perfluoroalkyl groups are widely used in organic synthesis and in the design of pharmaceutical molecules due to their specific physical properties, unique chemical reactivity and biological activity, [ (a) K.M uller, c.faeh, and f.diederich, Science,2017,317,1881; (b) s, Purser, p.r.moore, s.swallowb, and v.gouverneur, chem.soc.rev.,2008,37, 320; (c) e.p.gillis, k.j.eastman, m.d.hill, d.j.donnelly, and n.a.meanwell, j.med.chem.,2015,58,8315. Azide functional groups are not only present extensively in biologically active molecules, but are also important precursors for the synthesis of compounds containing amine and heterocyclic groups. Therefore, the compound with an ortho-trifluoromethyl substituted azide structure can be used for quickly synthesizing a large amount of compound libraries containing trifluoromethyl units through click reaction of an azide group, so as to be used for activity screening and drug development.
Starting from easily available olefins, the direct trifluoromethyl azidation is the most direct method for synthesizing trifluoromethyl azides. However, such reactions are currently limited to either the transition metal catalyzed or photocatalytic three-component reactions [ (a) g.dagouset, a. Carboni, e.magnier, and g.masson, org.lett.,2014,16,4340; (b) x.geng, f.lin, x.wang, and n.jiao, org.lett.,2017,19, 4738; (c) liu, q.guo, c.chen, m.wang, and z.xu, org.chem.front, 2018,5, 1522; (d) wang, x.qi, z.liang, p.chen, and g.liu, angelw.chem.int.ed., 2014, 53, 1881; (e) m.yang, w.wang, y.liu, l.feng, and x.ju, chi.j.chem., 2014,32, 833; (f) r.r. Karimov, a.sharma, and j.f.hartwig, ACS cent.sci.,2016,2, 715; (g) zhu, c.wang, q.qin, s.yruegas, c.d.martin, and h.xu, ACS cat., 2018,8, 5032; (h) y.zhang, x.han, j.zhao, j.qian, t.li, y.tang, and h. -y.zhang, adv.synth.cat., 2018,360,2659; (i) xiong, y.sun, and g.zhang, org.lett.,2018,20, 6250; (j) h.xiong, n.ramkumar, m. -f.chiou, w.jian, y.li, j. -h.su, x.zhang, and h.bao, nat.commun.,2019,10,122.]. These processes generally require the use of CF 3 I, Togni, etc. are expensive and difficult to store trifluoromethyl precursors, and produce stoichiometric by-products, thereby reducing the atom economy of the chemical reaction. Therefore, it is necessary to develop a synthesis method with mild reaction conditions and more direct, economical and efficient reaction.
Disclosure of Invention
Aiming at the technical problems in the prior art, the invention aims to provide a method for synthesizing an ortho-perfluoroalkyl substituted azide compound with mild reaction conditions and high efficiency.
The technical scheme provided by the invention is as follows:
a synthetic method of an ortho perfluoroalkyl substituted azide compound comprises the following steps:
radical initiator, N 3 SO 2 C n F 2n+1 Adding the ortho perfluoroalkyl group substituted azide compound II and the alkene I into a solvent, stirring, and separating and purifying after reaction to obtain an ortho perfluoroalkyl group substituted azide compound II;
wherein the free radical initiator is a peroxy compound or azo free radical initiator;
said N is 3 SO 2 C n F 2n+1 Wherein n is any integer from 1 to 10;
the structure of the olefin I is
Figure RE-GDA0003048558010000021
Wherein R is 1 、R 2 、R 3 、R 4 Each independently, optionally selected from hydrogen, alkyl, aryl-substituted alkyl, heteroatom-substituted alkyl, or halogen-substituted alkyl. Preferably, the alkyl group is C1-C18 alkyl, C6-C18 aryl substituted alkyl, heteroatom (N, O, S) substituted alkyl (C1-C12), halogen (F, Cl, Br, I) substituted alkyl (C1-C12).
Further, the structure of the peroxide compound free radical initiator is
Figure RE-GDA0003048558010000022
Wherein R is 5 、R 6 Independently selected from alkyl, aryl substituted ester group, alkyl substituted ester group or hydrogen. Preferably, R 5 、R 6 Independently selected from C1-C18 alkyl, C6-C18 aryl substituted ester group, C1-C18 alkyl substituted ester group or hydrogen.
The azo free radical initiator has the structure
Figure RE-GDA0003048558010000023
Wherein R is 7 、R 8 Independently selected from alkyl or cyano-substituted alkyl. Preferably, R 7 、R 8 Independently selected from C1-C18 alkyl or cyano-substituted C1-C18 alkyl.
Further, the radical initiator is selected from the group consisting of dilauryl peroxide (BPO), dilauryl peroxide (LPO), tert-butyl peroxybenzoate, di-tert-butyl peroxide (DTBP), tert-butyl hydroperoxide (TBHP), 2,6, 6-tetramethylpiperidine oxide (TEMPO), Azobisisobutyronitrile (AIBN), pentafluorobenzoyl peroxide, 4-trifluoromethylbenzoyl peroxide and 4-methylbenzoyl peroxide.
Further, said N 3 SO 2 C n F 2n+1 Wherein n is 1,2, 4, 10.
Further, the solvent is selected from one or a mixture of more of acetonitrile, chlorobenzene, dichloroethane, chloroform, dimethyl sulfoxide, ethyl acetate, acetone, ethylene glycol dimethyl ether, n-pentane, cyclohexane, n-hexane, dimethylformamide, methyl tert-butyl ether, cyclopentyl methyl ether, benzonitrile and 1, 4-dioxane.
Further, the structure of the perfluoroalkyl azide compound II is as follows:
Figure RE-GDA0003048558010000024
further, the olefins I and N 3 SO 2 C n F 2n+1 The molar ratio of (A) to (B) is 1: 1.0-5.0. Preferably, the olefins I and N 3 SO 2 C n F 2n+1 The molar ratio of (A) to (B) is 1: 1.0-2.5.
Further, the molar ratio of the olefin I to the radical initiator is 1: 0.05-5. Preferably, the molar ratio of olefin I to free radical initiator is from 1:0.1 to 0.2.
Further, the reaction temperature is 20-100 ℃. Preferably, the reaction temperature is 60-80 ℃.
Further, the reaction time is 0.1 to 24 hours. Preferably, the reaction time is 0.1 to 24 hours.
Further, the separation and purification method comprises column chromatography, thin layer chromatography, recrystallization or reduced pressure distillation.
Furthermore, the eluent used for the column chromatography is a mixed solution of petroleum ether and ethyl acetate, wherein the volume ratio of the petroleum ether to the ethyl acetate is 2-100: 1-0.
The synthesis method comprises the following steps: the raw material olefins I, N 3 SO 2 C n F 2n+1 Adding free radical initiator and organic solvent into a reaction bottle for heatingAfter 12 hours, cooling to room temperature, concentrating the solvent, separating and purifying to generate the ortho perfluoroalkyl substituted azide compound shown in II, wherein the reaction equation is as follows:
Figure RE-GDA0003048558010000031
preferably, the synthesis method is as follows: drying 10mL of sealed tube and magnetic stirring bar in advance, and then respectively adding raw materials I and N into the reaction tube under the protection of argon 3 SO 2 CF 3 And initiator, adding ethyl acetate, placing the whole reaction on a heating module at 80 ℃ for reaction, monitoring the whole reaction process by TLC, cooling to room temperature after the reaction is finished, concentrating the reaction liquid, using the mixed liquid of petroleum ether and ethyl acetate or the mixed liquid of petroleum ether and dichloromethane as eluent for the obtained crude product, and performing column chromatography separation by using 200-mesh 300-mesh silica gel as separation resin to obtain the ortho-trifluoromethyl substituted azide compound.
Compared with the prior art, the invention has the following beneficial effects:
(1) use of the invention N 3 SO 2 C n F 2n+1 The compounds act as perfluoroalkyl and azide precursors.
(2) The method has the advantages of simple and safe operation, easily obtained raw materials, mild reaction conditions, high atom economic efficiency and high reaction activity.
(3) The method avoids the use of a transition metal catalyst, has low economic cost, and can effectively reduce heavy metal residue and the pollution of the reaction to the environment.
Detailed Description
The technical solution of the present invention is further explained by the following embodiments. It should be understood by those skilled in the art that the examples are only for the understanding of the present invention and should not be construed as the specific limitation of the present invention.
Example 1
Taking 2-methyl-2- (1-pentenyl) diethyl malonate (1a) and trifluoromethyl sulfonyl azide as standard substrates, and researching the solvent and the concentration of the trifluoromethyl azide compound:
Figure RE-GDA0003048558010000041
Figure RE-GDA0003048558010000042
Figure RE-GDA0003048558010000051
wherein mol% refers to the relative molar amount, equiv represents the equivalent weight; the yield is nuclear magnetic yield, and the condition 6 is the optimal reaction condition.
Example 2
Study of temperature for the synthesis of trifluoromethyl azides with 2-methyl-2- (1-pentenyl) malonic acid diethyl ester (1a) and trifluoromethyl sulfonyl azide as standard substrates:
Figure RE-GDA0003048558010000052
Figure RE-GDA0003048558010000053
wherein mol% refers to the relative molar amount, equiv represents the equivalent weight; the yield is the nuclear magnetic yield, and the condition 2 is the optimal reaction condition.
Example 3
Research on the ratio of free radical initiators and reaction materials synthesized from trifluoromethyl azide compounds by using 2-methyl-2- (1-pentenyl) diethyl malonate (1a) and trifluoromethyl sulfonyl azide as standard substrates:
Figure RE-GDA0003048558010000061
Figure RE-GDA0003048558010000062
wherein mol% refers to the relative molar amount, equiv represents the equivalent weight; the yield is nuclear magnetic yield, the isolated yield is shown in parentheses, and condition 13 is the optimum reaction condition.
Example 4
The preparation method comprises the following elements: taking 10mL of dry reaction sealed tube with magnetic stirrer, pumping and filling the tube in argon atmosphere for three times, and adding reactant I (0.2mmol) and N 3 SO 2 CF 3 (0.3mmol, 0.3mL,1.0mmol/mL n-hexane solution) and 10 mol% IN-3(8.8mg,0.02mmol) IN 1mL ethyl acetate, were reacted IN an oil bath at 80 deg.C until the starting material reaction was complete as monitored by TLC (about 12 h). The system is recovered to room temperature, the reaction liquid is concentrated, the crude product is subjected to column chromatography separation by using a mixed liquid of petroleum ether and ethyl acetate or a mixed liquid of petroleum ether and dichloromethane as an eluent and using 200-300-mesh silica gel to obtain the trifluoromethyl azide compound
Example 5
In this example, diethyl 2-methyl 2- (4-azido-6,6, 6-trifluoromethyl) -2-malonate (diethyl 2- (4-azido-6,6,6-trifluorohexyl) -2-methylmalonate) was prepared, having the following structural formula:
Figure RE-GDA0003048558010000071
colorless oily liquid (61.7mg, 87% yield), R f ＝0.6(PE:EA＝20:1)。 1 H NMR(400MHz,CDCl 3 ) δ4.12(q,J＝7.1Hz,4H),3.63–3.52(m,1H),2.36–2.09(m,2H),1.88–1.73(m,2H),1.61–1.47 (m,2H),1.45–1.25(m,5H),1.18(t,J＝7.1Hz,6H)； 13 C NMR(100MHz,CDCl 3 )δ172.1,172.1, 125.4(q,J＝277.3Hz),61.3,56.4(q,J＝2.8Hz),53.4,38.6(q,J＝28.2Hz),35.0,34.9,20.6,19.9, 14.0； 19 F NMR(376MHz,CDCl 3 )δ–64.09(t,J＝10.8Hz)；HRMS(ESI + )calc’d for C 14 H 22 F 3 N 3 NaO 4 [M+Na] + :376.1455,found 376.1440.
Example 6
In this example, diethyl 2-methyl 2- (3-azido-5,5, 5-trifluoromethyl) -2-malonate (diethyl 2- (3-azido-5,5, 5-trifluoropropyl) -2-methylmalonate) was prepared, having the following structural formula:
Figure RE-GDA0003048558010000072
colorless oily liquid (55.8mg, 82% yield), R f ＝0.5(PE:EA＝20:1)。 1 H NMR(400MHz,CDCl 3 ) δ4.13(q,J＝7.1Hz,4H),3.63–3.43(m,1H),2.35–2.10(m,2H),2.06–1.92(m,1H),1.90–1.79 (m,1H),1.59–1.42(m,2H),1.35(s,3H),1.19(t,J＝7.1Hz,6H)； 13 C NMR(100MHz,CDCl 3 )δ 171.84,171.81,125.6(q,J＝278.1Hz),61.5,56.7(q,J＝3.1Hz),53.1,38.4(q,J＝28.4Hz),31.6, 29.6,20.0,14.0； 19 F NMR(376MHz,CDCl 3 )δ–64.15(t,J＝10.3Hz)；HRMS(ESI + )calc’d for C 13 H 21 F 3 N 3 O 4 [M+H] + :340.1479,found 340.1475.
Example 7
In this example, diethyl 2-methyl 2- (2-azido-4,4, 4-trifluoromethyl) -2-malonate (diethyl 2- (2-azido-4,4, 4-trifluorobutyl) -2-methylmalonate) was prepared, having the following structural formula:
Figure RE-GDA0003048558010000081
colorless oily liquid (38.3mg, 59% yield), R f ＝0.4(PE:EA＝50:1)。 1 H NMR(400MHz,CDCl 3 ) δ4.28–3.98(m,4H),3.80–3.67(m,1H),2.52–2.18(m,2H),2.13–1.92(m,2H),1.42(s,3H), 1.29–1.14(m,6H)； 13 C NMR(100MHz,CDCl 3 )δ171.6,171.4,125.4(q,J＝278.2Hz),61.9,61.7, 53.6(q,J＝2.7Hz),52.1,40.5,39.5(q,J＝28.3Hz),20.3,13.9； 19 F NMR(376MHz,CDCl 3 )δ– 64.08(t,J＝10.4Hz)；HRMS(ESI + )calc’d for C 12 H 18 F 3 N 3 NaO 4 [M+Na] + :348.1142,found 348.1139.
Example 8
In this example, ethyl 1- (2-azido-4,4, 4-trifluoromethyl) -2-cyclohexanone carboxylate (ethyl 1- (2-azido-4,4, 4-trifluorobutyl) -2-oxocyclohexane carboxylate) was prepared, which has the following formula:
Figure RE-GDA0003048558010000082
colorless oily liquid (38.3mg, 49% yield), R f ＝0.2(PE:EA＝20:1)，dr＝1:1。 1 H NMR(400 MHz,CDCl 3 )δ4.36–4.01(m,2H),4.00–3.77(m,0.5H)/3.72–3.57(m,0.5H),2.63–2.53(m, 1H),2.53–2.13(m,4.5H),2.06–1.85(m,1.5H),1.82–1.65(m,2H),1.64–1.57(m,2H),1.45– 1.34(m,1H),1.23(dq,J＝13.7,6.9Hz,3H)； 13 C NMR(100MHz,CDCl 3 )δ208.4/206.9, 171.6/170.9,125.5(q,J＝275.7Hz)/125.4(q,J＝278.5Hz),62.0/61.9,59.2/59.1,54.1(q,J＝2.5 Hz)/53.1(q,J＝3.0Hz),41.0/40.7,40.6/40.1,39.6/39.6,38.5/35.4,27.8/27.4,22.5/22.1,14.0/13.9； 19 F NMR(376MHz,CDCl 3 )δ–63.82(t,J＝10.4Hz),–64.03(t,J＝10.2Hz)；HRMS(ESI + )calc’d for C 13 H 18 F 3 N 3 NaO 3 [M+Na] + :344.1192,found 344.1190.
Example 9
In this example, 5-azido-7,7, 7-trifluoropentyl-2-one (5-azido-7,7,7-trifluoroheptan-2-one) was prepared, having the following structural formula:
Figure RE-GDA0003048558010000091
colorless oily liquid (14.5mg, 34% yield), R f ＝0.3(PE). 1 H NMR(400MHz,CDCl 3 )δ3.73–3.62 (m,1H),2.63(td,J＝7.4,6.9,1.6Hz,2H),2.40–2.25(m,2H),2.19(s,3H),2.01–1.88(m,1H), 1.81–1.66(m,1H)； 13 C NMR(100MHz,CDCl 3 )δ207.1,125.6(q,J＝277.1Hz),56.2(q,J＝2.9 Hz),39.3,38.9(q,J＝28.4Hz),30.2,28.6； 19 F NMR(376MHz,CDCl 3 )δ-64.05(t,J＝10.5Hz).
Example 10
In this example ((3-azido-5,5, 5-trifluoropentyl) oxy tert-butyldimethylsilane ((3-azido-5,5, 5-trifluoropentyl) oxy) (tert-butyl) dimethylsilyl, the formula of which is as follows:
Figure RE-GDA0003048558010000092
colorless oily liquid (23.3mg, 39% yield), R f ＝0.5(PE). 1 H NMR(400MHz,CDCl 3 )δ 1 H NMR (400MHz,Chloroform-d)δ3.98–3.85(m,1H),3.82–3.67(m,3H),2.34(ddd,J＝10.4,6.4,2.3 Hz,2H),1.92–1.77(m,1H),1.76–1.64(m,1H),0.90(s,13H),0.07(d,J＝2.8Hz,8H)； 13 C NMR (100MHz,CDCl 3 )δ125.9(q,J＝277.1Hz),58.9,54.1(q,J＝2.9Hz),38.9(q,J＝28.2Hz),37.6, 26.0,18.3； 19 F NMR(376MHz,CDCl 3 )δ-64.14(t,J＝10.5Hz).
Example 11
In this example, benzyl 4-azido-6,6, 6-trifluoromethylhexanoate (benzyl 4-azido-6,6,6-trifluorohexanoate) was prepared having the following structural formula:
Figure RE-GDA0003048558010000093
colorless oily liquid (70.7mg, 59% yield), R f ＝0.2(PE:EA＝30:1)。 1 H NMR(400MHz,CDCl 3 ) δ7.46–7.20(m,5H),5.07(s,2H),3.79–3.57(m,1H),2.46(t,J＝7.2Hz,2H),2.35–2.14(m,2H), 1.99–1.84(m,1H),1.80–1.65(m,1H).
Example 12
In this example, hexyl 4-azido-6,6, 6-trifluoromethylmethylbutyrate (4-azido-6,6,6-trifluorohexyl 3-methylbutanate) was prepared, having the formula:
Figure RE-GDA0003048558010000101
colorless oily liquid (38.5mg, 69% yield), R f ＝0.5(PE:EA＝20:1)。 1 H NMR(400MHz,CDCl 3 ) δ4.05(t,J＝5.6Hz,2H),3.66–3.56(m,1H),2.36–2.16(m,2H),2.13(d,J＝7.1Hz,2H),2.06– 1.99(m,1H),1.83–1.55(m,4H),0.89(d,J＝6.5Hz,6H)； 13 C NMR(100MHz,CDCl 3 )δ173.1, 125.6(q,J＝277.1Hz),63.3,56.5(q,J＝2.8Hz),43.4,38.7(q,J＝28.3Hz),31.4,25.7,25.0,22.4； 19 F NMR(376MHz,CDCl 3 )δ–64.07(t,J＝10.4Hz)；HRMS(ESI + )calc’d for C 11 H 19 F 3 NO 2 [M- N 2 +H] + :254.1362,found 254.1363.
Example 13
In this example, n-hexyl 4-azido-6,6, 6-trifluoromethylbenzoate (4-azido-6,6,6-trifluorohexyl benzoate) was prepared having the following structural formula:
Figure RE-GDA0003048558010000102
colorless oily liquid (47.9mg, 77% yield), R f ＝0.3(PE:EA＝10:1)。 1 H NMR(400MHz,CDCl 3 ) δ8.03(d,J＝7.7Hz,2H),7.57(t,J＝7.3Hz,1H),7.45(t,J＝7.6Hz,2H),4.39–4.32(m,2H),3.79 –3.65(m,1H),2.53–2.21(m,2H),2.00–1.98(m,1H),1.96–1.86(m,1H),1.84–1.70(m,2H).
Example 14
In this example, 4-azido-6,6, 6-trifluoro-n-hexyl 4-tosylate (4-azido-6,6,6-trifluorohexyl 4-methyllbenzene sulfonate) was prepared, having the following formula:
Figure RE-GDA0003048558010000111
colorless oily liquid (53.0mg, 76% yield), R f ＝0.4(PE:EA＝20:1)。 1 H NMR(400MHz,CDCl 3 ) δ7.72(d,J＝8.4Hz,2H),7.29(d,J＝8.2Hz,2H),4.12–3.78(m,2H),3.58–3.35(m,1H),2.38 (s,3H),2.31–2.01(m,2H),1.82–1.36(m,4H).
Example 15
In this example, diethyl 4-azido-6,6, 6-trifluoro-n-hexylphosphate (4-azido-6,6,6-trifluorohexyl dimethyl phosphate) was prepared, having the following structural formula:
Figure RE-GDA0003048558010000112
colorless oily liquid (43.9mg, 66% yield), R f ＝0.2(PE:EA＝20:1)。 1 H NMR(400MHz,CDCl 3 ) δ4.28–3.84(m,6H),3.76–3.47(m,1H),2.44–2.10(m,2H),1.85–1.52(m,4H),1.28(t,J＝6.6 Hz,6H)； 13 C NMR(100MHz,CDCl 3 )δ125.6(q,J＝277.2Hz),66.6(d,J＝5.8Hz),63.8(d,J＝ 5.9Hz),56.4(q,J＝2.7Hz),38.6(q,J＝28.3Hz),30.9,26.5(d,J＝7.1Hz),16.1(d,J＝6.6Hz)； 19 F NMR(376MHz,CDCl 3 )δ–64.09(d,J＝6.0Hz)；HRMS(ESI + )calc’d for C 10 H 19 F 3 N 3 NaO 4 P [M+Na] + :356.0957,found 356.0949.
Example 16
In this example, 2- (4-azido-6,6, 6-trifluoro-n-hexyl) isoindoline-1,3-dione (2- (4-azido-6,6,6-trifluorohexyl) isoindoline-1,3-dione) was prepared, which has the following structural formula:
Figure RE-GDA0003048558010000113
colorless oily liquid (51.3mg, 81% yield), R f ＝0.4(PE:EA＝20:1)。 1 H NMR(400MHz, CDCl 3 )δ7.84–7.74(m,2H),7.71–7.61(m,2H),3.75–3.54(m,3H),2.33–2.10(m,2H),1.91– 1.79(m,1H),1.78–1.68(m,1H),1.66–1.50(m,2H).
Example 17
In this example, 2- (3-azido-5,5, 5-trifluoro-n-pentyl) isoindoline-1,3-dione (2- (3-azido-5,5, 5-trifluoromethylindole) isoindoline-1,3-dione) was prepared, which has the following structural formula:
Figure RE-GDA0003048558010000121
colorless oily liquid (43.4mg, 70% yield), R f ＝0.4(PE:EA＝20:1)。 1 H NMR(400MHz,CDCl 3 ) δ8.01–7.72(m,2H),7.71–7.57(m,2H),3.86–3.69(m,2H),3.71–3.53(m,1H),2.44–2.17(m, 2H),1.98–1.83(m,1H),1.85–1.70(m,1H)
Example 18
In this example, n-hexyl (4-azido-6,6, 6-trifluoromethyl) 2-furoate (4-azido-6,6,6-trifluorohexyl furan-2-carboxylate) was prepared, having the formula:
Figure RE-GDA0003048558010000122
colorless oily liquid (22.3mg, 38% yield), R f ＝0.5(PE:EA＝10:1)。 1 H NMR(400MHz,CDCl 3 ) δ7.58(dd,J＝1.8,0.8Hz,1H),7.19(dd,J＝3.5,0.9Hz,1H),6.52(dd,J＝3.5,1.8Hz,1H),4.52– 4.15(m,2H),3.95–3.31(m,1H),2.48–2.20(m,2H),2.03–1.82(m,2H),1.82–1.64(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ158.6,146.5,144.5,125.6(q,J＝276.9Hz),118.1,111.9,64.0,56.5(d, J＝2.9Hz),38.7(q,J＝28.3Hz),31.4,25.0； 19 F NMR(376MHz,CDCl 3 )δ–64.04(t,J＝10.5Hz)； HRMS(ESI + )calc’d for C 11 H 12 F 3 N 3 NaO 3 [M+Na] + :314.0723,found 314.0726.
Example 19
In this example, n-hexyl (4-azido-5-trifluoromethyl) 2-thiophenoate (4-azido-6,6, 6-trifluorohexythiophene-2-carboxylate) was prepared, which has the following structural formula:
Figure RE-GDA0003048558010000131
colorless oily liquid (25.1mg, 41% yield), R f ＝0.4(PE:EA＝10:1)。 1 H NMR(400MHz,CDCl 3 ) δ7.80(dd,J＝3.8,1.3Hz,1H),7.57(dd,J＝5.0,1.3Hz,1H),7.11(dd,J＝5.0,3.7Hz,1H),4.62– 4.15(m,2H),3.86–3.60(m,1H),2.79–2.14(m,2H),2.04–1.67(m,4H)； 13 C NMR(100MHz, CDCl 3 )δ162.1,133.6,133.5,132.6,127.9,125.6(d,J＝276.9Hz),64.2,56.4(q,J＝2.6Hz),38.7 (q,J＝28.3Hz),31.4,25.0； 19 F NMR(376MHz,CDCl 3 )δ–64.02(d,J＝11.0Hz)；HRMS(ESI + ) calc’d for C 11 H 13 F 3 NO 2 S[M-N 2 +H] + :280.0614,found 280.0615.
Example 20
In this example, n-hexyl (4-azido-5-trifluoromethyl) 2-pyridinecarboxylate (4-azido-6,6,6-trifluorohexyl picolinate) was prepared, having the following structural formula:
Figure RE-GDA0003048558010000132
colorless oily liquid (33.2mg, 55% yield), R f ＝0.2(PE:EA＝3:1)。 1 H NMR(400MHz,CDCl 3 ) δ8.70(d,J＝4.7Hz,1H),8.07(d,J＝7.8Hz,1H),7.80(t,J＝7.7Hz,1H),7.43(dd,J＝7.6,4.7Hz, 1H),4.49–4.31(m,J＝6.4Hz,2H),3.72–3.65(m,1H),2.32–2.20(m,2H),2.08–1.84(m,2H), 1.76–1.58(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ165.1,149.9,147.8,137.2,127.1,125.6(q,J＝ 278.1Hz),125.2,65.0,56.5(q,J＝2.9Hz),38.7(q,J＝28.4Hz),31.4,25.1； 19 F NMR(376MHz, CDCl 3 )δ–64.05(t,J＝11.0Hz)；HRMS(ESI + )calc’d for C 12 H 13 F 3 N 4 NaO 2 [M+Na] + :325.0883, found 325.0882.
Example 21
In this example, 4-azido-6,6, 6-trifluoro-n-hexyl-3-chloro-2, 2-dimethylpropionate (4-azido-6,6,6-trifluorohexyl 3-chloro-2,2-dimethylpropanoate) was prepared having the following structural formula:
Figure RE-GDA0003048558010000133
colorless oil (41.9mg, 66% yield), R f ＝0.3(PE:EA＝20:1)。 1 H NMR(400MHz,CDCl 3 ) δ4.24–4.00(m,2H),3.70–3.56(m,1H),3.54(s,2H),2.39–2.11(m,2H),1.91–1.47(m,4H), 1.22(s,6H)； 13 C NMR(100MHz,CDCl 3 )δ174.9,125.6(q,J＝277.2Hz),64.0,56.3(q,J＝2.8 Hz),52.0,44.7,38.6(q,J＝28.3Hz),31.2,24.9,23.5,23.3； 19 F NMR(376MHz,CDCl 3 )δ–64.05 (t,J＝10.7Hz)；HRMS(ESI + )calc’d for C 11 H 18 ClF 3 NO 2 [M-N 2 +H] + :288.0973,found 288.0975.
Example 22
In this example, 4-azido-6,6, 6-trifluoro-n-hexyl-3-bromopropionate (4-azido-6,6,6-trifluorohexyl 3-bromopropionate) was prepared, having the following structural formula:
Figure RE-GDA0003048558010000141
colorless oil (53.0mg, 80% yield), R f ＝0.4(PE:EA＝20:1)。 1 H NMR(400MHz,CDCl 3 ) δ4.16–3.99(m,2H),3.72–3.56(m,1H),3.40(t,J＝6.4Hz,2H),2.45(t,J＝7.2Hz,2H),2.34– 2.16(m,2H),2.16–2.04(m,2H),1.85–1.51(m,4H)； 13 C NMR(100MHz,CDCl 3 )δ172.5,125.6 (q,J＝277.4Hz),63.7,56.4(q,J＝2.9Hz),38.6(q,J＝28.2Hz),32.7,32.3,31.3,27.6,24.9； 19 F NMR(376MHz,CDCl 3 )δ–64.06(t,J＝10.4Hz)；HRMS(ESI + )calc’d for C 10 H 15 BrF 3 N 3 NaO 2 [M+Na] + :368.0192,found 368.0187.
Example 23
In this example, 1- (3-azido-5,5, 5-trifluoro-n-pentyl) -2-bromobenzene (1- (3-azido-5,5, 5-trifluoropenthyl) -2-bromobenzene) was prepared having the following structural formula:
Figure RE-GDA0003048558010000142
colorless oil (31.6mg, 49% yield), R f ＝0.4(PE:EA＝20:1)。 1 H NMR(400MHz,CDCl 3 ) δ7.66–7.60(m,1H),7.41–7.24(m,2H),7.23–7.12(m,1H),3.78–3.72(m,1H),3.10–2.97(m, 1H),2.98–2.87(m,1H),2.59–2.28(m,2H),2.18–1.81(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ 138.6,132.1,129.4,127.2,126.7,124.6(q,J＝278.4Hz),123.3,55.2(q,J＝2.4Hz),37.6(q,J＝28.3Hz),33.7,31.4； 19 F NMR(376MHz,CDCl 3 )δ–63.97(t,J＝10.4Hz)；HRMS(ESI + )calc’d for C 11 H 11 BrF 3 NaN[M-N 2 +Na] + :294.0100,found 294.0096.
Example 24
In this example, 3-azido-1,1,1-trifluoroundecane (3-azido-1,1, 1-trifluoroundecan) was prepared having the following structural formula:
Figure RE-GDA0003048558010000151
colorless oil (29.3mg, 58% yield), R f ＝0.8(PE)。 1 H NMR(400MHz,CDCl 3 )δ3.65–3.58 (m,1H),2.38–2.20(m,2H),1.65–1.54(m,2H),1.52–1.25(m,12H),0.89(t,J＝6.8Hz,3H).
Example 25
In this example, 3-azido-1,1, 1-trifluorododecane (3-azido-1,1, 1-trifluorotriecane) was prepared, having the following structural formula:
Figure RE-GDA0003048558010000152
colorless oil (33.0mg, 62% yield), R f ＝0.8(PE)。 1 H NMR(400MHz,CDCl 3 )δ3.65– 3.58(m,1H),2.39–2.19(m,2H),1.62–1.58(m,2H),1.51–1.23(m,14H),0.881(t,J＝6.8Hz, 3H).
Example 26
In this example, 3-azido-1,1, 1-trifluorohexadecane (3-azido-1,1, 1-trifluoroheptadecene) was prepared, which has the following structural formula:
Figure RE-GDA0003048558010000153
colorless oil (39.8mg, 59% yield), R f ＝0.8(PE)。 1 H NMR(400MHz,CDCl 3 )δ3.65–3.58 (m,1H),2.36–2.21(m,2H),1.66–1.54(m,2H),1.45–1.26(m,24H),0.88(t,J＝6.8Hz,3H)
Example 27
In this example, n-pentyl (3-azido-5,5, 5-trifluoro-3-methylbenzoate) (3-azido-5,5, 5-trifluo-3-methyl pentanyl benzoate) was prepared, which has the following structural formula:
Figure RE-GDA0003048558010000161
colorless oil (49.1mg, 81% yield), R f ＝0.4(PE:EA＝20:1)。 1 H NMR(400MHz,CDCl 3 ) δ7.98–7.92(m,2H),7.53–7.47(m,1H),7.37(t,J＝7.7Hz,2H),4.49–4.31(m,2H),2.43–2.32 (m,2H),2.10–1.99(m,2H),1.47(s,3H).
Example 28
In this example, (2-azido-4,4, 4-trifluoro-2-methyl-n-butyl) benzene ((2-azido-4,4, 4-trifluo-2-methylbutanyl) bezene) was prepared having the following formula:
Figure RE-GDA0003048558010000162
colorless oil (37.4mg, 77% yield), R f ＝0.8(PE)。 1 H NMR(400MHz,CDCl 3 )δ7.42– 7.25(m,3H),7.25–7.16(m,2H),2.89(d,J＝2.5Hz,2H),2.31(q,J＝11.0Hz,2H),1.44(s,3H).
Example 29
In this example, (3-azido-3- (2,2, 2-trifluoroethyl) n-hexyl) benzene ((3-azido-3- (2,2, 2-trifluoroethyl) hexyl) bezene) was prepared having the following structural formula:
Figure RE-GDA0003048558010000163
colorless oil (38.0mg, 71% yield), R f ＝0.5(PE)。 1 H NMR(400MHz,CDCl 3 )δ7.51–7.28 (m,2H),7.27–7.15(m,3H),2.74–2.62(m,2H),2.41(q,J＝11.0Hz,2H),2.02–1.88(m,2H), 1.79–1.67(m,2H),1.52–1.37(m,2H),1.00(t,J＝7.3Hz,3H)； 13 C NMR(100MHz,CDCl 3 )δ 140.9,128.7,128.3,126.3,125.6(q,J＝278.9Hz),63.2,39.4(q,J＝27.5Hz),39.0,38.8,30.0,16.9, 14.2； 19 F NMR(376MHz,CDCl 3 )δ–60.56(t,J＝11.1Hz)；HRMS(ESI + )calc’d for C 14 H 18 F 3 N 3 Na [M+Na] + :308.1345,found 308.1346.
Example 30
In this example, methyl 2-azido-4,4, 4-trifluoro-3, 3-dimethylbutyl 3-methylbutyrate (2-azido-4,4, 4-trifluo-3, 3-dimethylbutyl 3-methylbutanate) was prepared having the following formula:
Figure RE-GDA0003048558010000171
colorless oily liquid (31.9mg, 60% yield), R f ＝0.3(PE:EA＝20:1)。 1 H NMR(400MHz,CDCl 3 ) δ4.35(dd,J＝12.3,4.0Hz,1H),4.23(dd,J＝12.3,5.9Hz,1H),2.41(tt,J＝9.6,3.6Hz,1H),2.19 –2.11(m,2H),2.03(dh,J＝7.6,6.5Hz,1H),1.44(s,3H),1.36(s,3H),0.89(d,J＝6.6Hz,6H)； 13 C NMR(100MHz,CDCl 3 )172.6,126.1(q,J＝282.5Hz),60.6,59.5(q,J＝2.9Hz),51.0(q,J＝ 24.4Hz),43.2,26.1,25.6,24.0,22.3； 19 F NMR(376MHz,CDCl 3 )δ-63.52(d,J＝9.5Hz)；HRMS (ESI + )calc’d for C 11 H 19 F 3 NO 2 + [M-N 2 +H] + :254.1362,found 254.1365.
Example 31
In this example, methyl 3-azido-5,5,5-trifluoro-3, 4,4-trimethylpentyl 3-methylbutyrate (3-azido-5,5, 5-trifluo-3, 4, 4-trimethypenthyl 3-methylbutanate) was prepared having the following structural formula:
Figure RE-GDA0003048558010000172
colorless oily liquid, HRMS (ESI) + )calc’d for C 13 H 23 F 3 N 3 O 2 + [M+H] + :310.1737,found 310.1740.
Example 32
In this example, 4-azido-6,6, 6-trifluoro-n-hexyl 2- (4-isobutylphenyl) acid ester (4-azido-6,6,6-trifluorohexyl 2- (4-isobutylphenyl) propanoate) was prepared having the following structural formula:
Figure RE-GDA0003048558010000181
colorless oily liquid (58.3mg, 76% yield), R f ＝0.4(PE:EA＝20:1)。 1 H NMR(400MHz,CDCl 3 ) δ7.12(d,J＝8.0Hz,2H),7.02(d,J＝7.9Hz,2H),4.10–3.91(m,2H),3.62(q,J＝7.2Hz,1H), 3.55–3.41(m,1H),2.37(d,J＝7.2Hz,2H),2.28–1.98(m,2H),1.88–1.56(m,3H),1.43–1.39 (m,5H),0.82(d,J＝6.6Hz,6H)； 13 C NMR(100MHz,CDCl 3 )δ174.7,140.7,137.702/137.695, 129.4,127.1,125.5(q,J＝277.1Hz),63.6/63.5,56.3–56.2(m),45.1,45.13/44.98,38.5(q,J＝28.3 Hz),31.2/31.1,30.2,24.9/24.8,22.4,18.3； 19 F NMR(376MHz,CDCl 3 )δ–64.08(t,J＝10.7Hz)； HRMS(ESI + )calc’d for C 19 H 26 F 3 N 3 NaO 2 [M+Na] + :408.1869,found 408.1870.
Example 33
In this example, 4-Azido-6,6, 6-trifluoro-n-hexyl 2- (4-benzoylphenyl) acid ester 4-Azido-6,6,6-trifluorohexyl 2- (4-benzoylphenyl) propanoate was prepared having the following structural formula:
Figure RE-GDA0003048558010000182
colorless oily liquid (53.2mg, 64% yield), R f ＝0.2(PE:EA＝20:1)，dr＝1:1。 1 H NMR (400MHz,CDCl 3 )δ7.84–7.71(m,3H),7.66(d,J＝7.5Hz,1H),7.60(t,J＝7.3Hz,1H),7.55– 7.42(m,4H),4.16–4.07(m,2H),3.81(q,J＝7.2Hz,1H),3.61–3.56(m,1H),2.36–2.10(m,2H), 1.87–1.75(m,1H),1.74–1.68(m,1H),1.61–1.44(m,5H)； 13 C NMR(100MHz,CDCl 3 )δ196.5, 174.0,140.9/140.8,138.0,137.4,132.6,131.47/131.46,130.1,129.14/129.11,128.6,128.4,125.6(q, J＝277.5Hz),64.00/63.95,56.3(q,J＝3.2Hz),45.4,38.6(q,J＝28.3Hz),31.21/31.17,24.89/24.86, 18.3； 19 F NMR(376MHz,CDCl 3 )δ–64.02(t,J＝10.5Hz)；HRMS(ESI + )calc’d for C 22 H 23 F 3 N 3 O 3 [M+H] + :434.1686,found 434.1689.
Example 34
In this example, 4-azido-6,6, 6-trifluoro-n-hexylnicotinate (4-azido-6,6,6-trifluorohexyl nicotinate) was prepared having the following structural formula:
Figure RE-GDA0003048558010000191
colorless oily liquid (36.0mg, 60% yield), R f ＝0.4(PE:EA＝5:1)。 1 H NMR(400MHz,CDCl 3 ) δ9.22(s,1H),8.79(s,1H),8.31(d,J＝7.9Hz,1H),7.42(dd,J＝8.0,4.8Hz,1H),δ4.41(t,J＝6.5 Hz,2H),3.79–3.64(m,1H),2.48–2.26(m,2H),2.10–1.68(m,4H)； 13 C NMR(100MHz,CDCl 3 ) δ165.1,153.4,150.7,137.3,126.1,125.5(q,J＝278.0Hz)123.5,64.5,56.4(q,J＝3.6Hz),38.7(q, J＝28.5Hz),31.3,25.0； 19 F NMR(376MHz,CDCl 3 )δ–64.00(t,J＝10.4Hz)；HRMS(ESI + )calc’d for C 12 H 14 F 3 N 4 O 2 [M+H] + :303.1063,found 303.1063.
Example 35
In this example, 4-azido-6,6, 6-trifluoro-N-hexyl 4- (N, N-diisopropylsulfonyl) benzoate (4-azido-6,6,6-trifluorohexyl 4- (N, N-dipropylsulfamoyl) benzoate) was prepared having the following formula:
Figure RE-GDA0003048558010000192
colorless oily liquid (55.3mg, 66% yield), R f ＝0.5(PE:EA＝5:1)。 1 H NMR(400MHz,CDCl 3 ) δ8.07(d,J＝8.4Hz,2H),7.81(d,J＝8.4Hz,2H),4.33(t,J＝6.3Hz,2H),3.69–3.63(m,1H), 3.08–2.95(m,4H),2.41–2.15(m,2H),2.02–1.89(m,1H),1.88–1.79(m,1H),1.77–1.60(m, 2H),1.55–1.40(m,4H),0.80(t,J＝7.4Hz,6H)； 13 C NMR(100MHz,CDCl 3 )δ165.2,144.4,133.3, 130.2,127.1,125.5(q,J＝277.0Hz),64.7,56.4(q,J＝3.1Hz),49.9,38.6(q,J＝28.4Hz),31.3, 25.0,21.9,11.1； 19 F NMR(376MHz,CDCl 3 )δ–64.00(t,J＝10.4Hz)；HRMS(ESI + )calc’d for C 19 H 27 F 3 N 4 NaO 4 S[M+Na] + :487.1597,found 487.1604.
Example 36
In this example, 4-azido-6,6, 6-trifluoro-n-hexyl 2-methoxybenzoate (4-azido-6,6,6-trifluorohexyl 2-methoxybenzoate) was prepared, which has the following structural formula:
Figure RE-GDA0003048558010000201
colorless oily liquid (44.8mg, 62% yield), R f ＝0.5(PE:EA＝10:1)。 1 H NMR(400MHz,CDCl 3 ) δ7.77(dd,J＝7.9,1.8Hz,1H),7.68–7.43(m,1H),7.14–6.82(m,2H),4.53–4.16(m,2H),3.89 (s,3H),3.79–3.63(m,1H),2.64–2.23(m,2H),2.08–1.71(m,4H)； 13 C NMR(100MHz,CDCl 3 ) δ166.2,159.2,133.7,131.6,125.6(q,J＝276.9Hz),120.2,119.9,112.0,63.9,56.5(q,J＝2.8Hz), 55.9,38.7(q,J＝28.3Hz),31.5,25.1； 19 F NMR(376MHz,CDCl 3 )δ–64.03(t,J＝10.4Hz)；HRMS (ESI + )calc’d for C 14 H 16 F 3 N 3 NaO 3 [M+Na] + :354.1036,found 354.1039.
Example 37
In this example, 2- (4-azido-6,6, 6-trifluoro-n-hexyl) benzisothiazole 3-one dioxide (2- (4-azido-6,6,6-trifluorohexyl) benzo [ d ] isothiazol-3(2H) -one 1,1-dioxide) was prepared having the following structural formula:
Figure RE-GDA0003048558010000202
colorless oily liquid (47.1mg, 65% yield), R f ＝0.4(PE:EA＝10:1)。 1 H NMR(400MHz,CDCl 3 ) δ8.11–7.95(m,1H),7.90–7.70(m,3H),3.76(t,J＝7.0Hz,2H),3.71–3.57(m,1H),2.36–2.14 (m,2H),2.06–1.94(m,1H),1.95–1.82(m,1H),1.76–1.54(m,2H)； 13 C NMR(100MHz,CDCl 3 ) δ159.1,137.6,134.9,134.5,127.2,125.6(q,J＝278.0Hz),125.3,121.0,56.3(q,J＝2.9Hz),38.6 (q,J＝28.4Hz),38.6,31.9,24.7； 19 F NMR(376MHz,CDCl 3 )δ–64.08(t,J＝10.5Hz)；HRMS (ESI + )calc’d for C 13 H 14 F 3 N 2 O 3 S[M-N 2 +H] + :335.0672,found 335.0673.
Example 38
In this example, 4-azido-6,6, 6-trifluoro-n-hexyl 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-dihydroquinoline-3-carboxylate (4-azido-6,6, 6-trifluorhexyl 7-chloro-1-cyclopropy-6-fluoro-4-oxo-1, 4-dihydroquino line-3-carboxylate) was prepared, having the following structural formula:
Figure RE-GDA0003048558010000211
colorless oily liquid (49.8mg, 50% yield), R f ＝0.2(PE:EA＝1:1)。 1 H NMR(400MHz,CDCl 3 ) δ8.56(s,1H),8.18(d,J＝9.0Hz,1H),8.00(d,J＝5.9Hz,1H),4.45–4.23(m,2H),3.82–3.71(m, 1H),3.49–4.43(m,1H),2.39–2.30(m,2H),2.07–1.81(m,3H),1.81–1.69(m,1H),1.43–1.33 (m,2H),1.16(s,2H)； 13 C NMR(100MHz,CDCl 3 )δ172.76/172.74,165.4,155.8(d,J＝250.7Hz), 149.0,137.2,129.9(d,J＝2.9Hz),128.7(d,J＝6.2Hz),127.04/127.01,125.7(q,J＝278.2Hz), 64.2,56.5(q,J＝2.5Hz),38.6(q,J＝28.1Hz),34.8,31.5,25.0,8.3； 19 F NMR(376MHz,CDCl 3 )δ–63.98(t,J＝10.5Hz),–(114.54–125.63)(m)；HRMS(ESI + )calc’d for C 19 H 18 ClF 4 N 4 O 3 [M+H] + : 461.0998,found 461.0998.
Example 39
In this example, (3r,5r,7r) -4-azido-6,6, 6-trifluoro-n-hexyladamantane-1-carboxylate ((3r,5r,7r) -4-azido-6,6, 6-trifluorohexyladamantane-1-carboxylate) was prepared having the following structural formula:
Figure RE-GDA0003048558010000212
colorless oily liquid (56.7mg, 82% yield), R f ＝0.5(PE:EA＝20:1)，dr＝1:1。 1 H NMR(400 MHz,CDCl 3 )δ4.08(t,J＝5.8Hz,2H),3.70–3.65(tt,J＝8.4,4.2Hz,1H),2.45–2.20(m,2H), 2.01(s,3H),1.91–1.81(m,7H),1.78–1.59(m,9H)； 13 C NMR(100MHz,CDCl 3 )δ177.7,125.6 (q,J＝277.2Hz),63.1,56.4(q,J＝2.9Hz),40.7,38.9,38.6(q,J＝28.5Hz),36.5,31.3,27.9,24.9； 19 F NMR(376MHz,CDCl 3 )δ–64.03(t,J＝10.5Hz)；HRMS(ESI + )calc’d for C 17 H 25 F 3 N 3 O 2 [M+H] + :360.1893,found 360.1889.
Example 40
In this example, 4-azido-6,6, 6-trifluoro-n-hexyl (1S,4R) -7,7-dimethyl-2-oxo [2.2.1] heptyl-1-methanesulfonate (4-azido-6,6,6-trifluorohexyl ((1S,4R) -7,7-dimethyl-2-oxobicyclo [2.2.1] heptan-1-yl) methanesulfonate) was prepared, having the formula:
Figure RE-GDA0003048558010000221
colorless oily liquid (64.3mg, 78% yield), R f ＝0.5(PE:EA＝20:1)，dr＝1:1。 1 H NMR(400 MHz,CDCl 3 )δ4.45–4.09(m,2H),3.81–3.57(m,1H),3.52(d,J＝15.1Hz,1H),2.93(d,J＝15.1 Hz,1H),2.54–2.14(m,4H),2.12–1.94(m,2H),1.95–1.52(m,6H),1.51–1.31(m,1H),1.04(s, 3H),0.81(s,3H)； 13 C NMR(100MHz,CDCl 3 )δ214.6,126.1(q,J＝271.0Hz),69.6,57.9,56.3(q, J＝2.8Hz),48.1,46.8,42.7,42.5,38.6(q,J＝28.3Hz),30.9,26.9,25.6,24.9,19.68/19.65； 19 F NMR (376MHz,CDCl 3 )δ–64.01(t,J＝10.4Hz)；HRMS(ESI + )calc’d for C 16 H 24 F 3 N 3 NaO 4 S[M+Na] + : 434.1332,found 434.1330.
EXAMPLE 41
In this example ((1S,2R,4S) -1,7,7-trimethyl 2-oxo [2.2.1] heptyl 4-azido-6,6, 6-trifluoro-n-hexyl ester (((1S,2R,4S) -1,7, 7-trimethylbycol [2.2.1] heptan-2-yl 4-azido-6,6, 6-trifluohexan-oate) was prepared, having the formula:
Figure RE-GDA0003048558010000222
colorless oil (49.1mg, 71% yield), R f ＝0.6(PE:EA＝20:1)，dr＝1:1。 1 H NMR(400 MHz,CDCl 3 )δ5.12–4.70(m,1H),3.92–3.65(m,1H),2.50(t,J＝7.2Hz,2H),2.43–2.23(m, 3H),2.08–1.70(m,4H),1.68(t,J＝4.5Hz,1H),1.38–1.17(m,2H),0.96(dt,J＝13.8,3.3Hz, 1H),0.90(s,3H),0.87(s,3H),0.83/0.83(s,3H)； 13 C NMR(100MHz,CDCl 3 )δ172.6,125.5(q,J ＝277.2Hz),80.5,56.1(q,J＝2.9Hz),48.8,47.8,44.9,38.8(q,J＝28.4Hz),36.8,30.6,30.0,28.0, 27.1,19.7,18.8,13.5； 19 F NMR(376MHz,CDCl 3 )δ–64.07(t,J＝10.8Hz)；HRMS(ESI + )calc’d for C 16 H 24 F 3 N 3 NaO 2 [M+Na] + :370.1713,found 370.1709.
Example 42
In this example, (1R,2S,5R) -2-isopropyl-5-methylcyclohexyl 4-azido-6,6, 6-trifluoro-n-hexyl ester ((1R,2S,5R) -2-isoproyl-5-methyycyclohexyl 4-azido-6,6,6-trifluorohexanoate) was prepared having the following structural formula:
Figure RE-GDA0003048558010000231
colorless oil (48.3mg, 72% yield), R f ＝0.5(PE:EA＝50:1)，dr＝1:1。 1 H NMR(400 MHz,CDCl 3 )δ4.74–4.68(m,1H),3.84–3.62(m,1H),2.46(t,J＝7.2Hz,2H),2.38–2.24(m,2H), 2.06–1.89(m,2H),1.89–1.77(m,2H),1.72–1.64(m,2H),1.54–1.43(m,1H),1.43–1.32(m, 1H),1.18–0.94(m,2H),0.95–0.82(m,7H),0.75(d,J＝7.0Hz,3H)； 13 C NMR(100MHz,CDCl 3 ) δ171.9,125.5(q,J＝277.0Hz),74.7,56.2–56.1(m),47.0,40.89/40.86,38.8(q,J＝28.4Hz),34.2, 31.4,30.6,30.0,26.4/26.3,23.4,22.0,20.7,16.24/16.23； 19 F NMR(376MHz,CDCl 3 )δ–64.112(t, J＝7.1Hz),δ–64.122(t,J＝14.3Hz)；HRMS(ESI + )calc’d for C 16 H 27 F 3 NO 2 [M-N 2 +H]:322.1988, found 322.1991.
Example 43
In this example, (4-azido-6,6, 6-trifluorooxyhexyl 2- ((tert-butoxycarbonyl) amino) acetic acid ((4-azido-6, 6,6-trifluorohexyl 2- ((tert-butoxycarbonyl) amino) acetate) was prepared, which has the following structural formula:
Figure RE-GDA0003048558010000232
colorless oil (47.6mg, 67% yield), R f ＝0.4(PE:EA＝5:1)。 1 H NMR(400MHz,CDCl 3 )δ 4.98(brs,1H),4.18–4.03(m,2H),3.84(d,J＝5.6Hz,2H),3.73–3.43(m,1H),2.40–2.13(m, 2H),1.99–1.52(m,4H),1.38(s,9H)； 13 C NMR(100MHz,CDCl 3 )δ170.4,155.7,125.5(q,J＝ 277.3Hz),80.1,64.4,56.4(q,J＝3.3Hz),42.4,38.7(q,J＝28.4Hz),31.2,28.3,24.9； 19 F NMR (376MHz,CDCl 3 )δ–64.05(t,J＝10.7Hz)；HRMS(ESI + )calc’d for C 13 H 21 F 3 N 4 NaO 4 [M+Na] + : 377.1407,found 377.1405.
Example 44
In this example, 4- ((S) -2- ((tert-butoxycarbonyl) amino) -3-methoxy-3-oxopentyl) phenyl 4-azido-6,6, 6-trifluorooxyhexyl (4- ((S) -2- ((tert-butoxycarbonyl) amino) -3-methoxy-3-oxopropyl) phenyl 4-azido-6,6,6-trifluorohexanoate) was prepared having the following structural formula:
Figure RE-GDA0003048558010000241
colorless oil (52.2mg, 58% yield), R f ＝0.4(PE:EA＝5:1)，dr＝1:1。 1 H NMR(400MHz, CDCl 3 )δ7.14(d,J＝8.1Hz,2H),7.02(d,J＝8.4Hz,2H)5.00(d,J＝7.8Hz,1H),4.60–4.55(m, 1H),3.85–3.79(m,1H),3.71(s,3H),3.14–3.01(m,2H),2.74(t,J＝7.2Hz,2H),2.50–2.26(m, 2H),2.16–1.99(m,1H),1.97–1.83(m,1H),1.41(s,9H)； 13 C NMR(100MHz,CDCl 3 )δ172.2, 170.9,155.1,149.5,133.9,130.4,125.5(q,J＝277.3Hz),121.5,80.1,56.2(q,J＝2.7Hz),54.4, 52.3,38.8(q,J＝28.4Hz),37.7,30.4,29.8,28.3； 19 F NMR(376MHz,CDCl 3 )δ–63.99(t,J＝10.4 Hz)；HRMS(ESI + )calc’d for C 21 H 27 F 3 N 4 NaO 6 [M+Na] + :511.1775,found 511.1778.
Example 45
In this example, (2R) -2- (4-azido-6,6, 6-trifluorooxyhexyl) 1-tert-butylpyrrolidine-1, 2-dicarbocarboxylate ((2R) -2- (4-azido-6,6,6-trifluorohexyl)1-tert-butyl pyrolidine-1, 2-dicarboxylate) was prepared, which has the following formula:
Figure RE-GDA0003048558010000242
colorless oil (45.3mg, 57% yield), R f ＝0.5(PE:EA＝5:1)。 1 H NMR(400MHz,CDCl 3 ) δ4.32–4.03(m,3H),3.72–3.54(m,1H),3.53–3.26(m,2H),2.38–2.09(m,3H),1.97–1.75(m, 4H),1.74–1.51(m,3H),1.36(d,J＝17.8Hz,9H)； 13 C NMR(100MHz,CDCl 3 )δ173.2/173.1, 154.5/153.8,125.6(q,J＝267.5Hz)/125.6(q,J＝289.0Hz)80.1/79.9,64.0,63.8,59.1/58.9,56.54 –56.29(m),46.6/46.3,38.6(q,J＝28.3Hz)/38.5(q,J＝28.6Hz),38.7/38.5,31.3,31.2,31.1/30.9, 30.0,28.4,28.3,25.0,24.4,23.6； 19 F NMR(376MHz,CDCl 3 )δ–(63.97–64.14)(m)；HRMS(ESI + ) calc’d for C 16 H 25 F 3 N 4 NaO 4 [M+Na] + :417.1720,found 417.1719.
Example 46
In this example, (2S) -4-azido-6,6, 6-trifluorooxyhexyl 2- ((tert-butoxycarbonyl) amine) -3-methylbutyrate ((2S) -4-azido-6,6,6-trifluorohexyl 2- ((tert-butyloxycarbonyl) amino) -3-methylbutan-oate) was prepared having the following structural formula:
Figure RE-GDA0003048558010000251
colorless oily liquid (50.9mg, 64% yield), R f ＝0.4(PE:EA＝5:1)，dr＝1:1。 1 HNMR(400 MHz,CDCl 3 )δ4.99(d,J＝8.4Hz,1H),4.29–3.99(m,3H),3.69–3.57(m,1H),2.45–2.20(m, 2H),2.20–1.99(m,1H),1.95–1.54(m,4H),1.43(s,9H),0.95(d,J＝6.9Hz,3H),0.88(d,J＝6.9 Hz,3H)； 13 C NMR(100MHz,CDCl 3 )δ172.5,155.7,125.5(q,J＝277.0Hz),79.8,64.13/64.10, 58.6,56.4(q,J＝2.9Hz),38.6(q,J＝29.8Hz),38.6(q,J＝28.2Hz),31.3/31.2,28.3,24.94/24.89, 19.0,17.6； 19 F NMR(376MHz,CDCl 3 )δ–(64.03–64.10)(m)；HRMS(ESI + )calc’d for C 16 H 27 F 3 N 4 NaO 4 [M+Na] + :419.1877,found 419.1868.
Example 47
In this example, (2S) -4-azido-6,6, 6-trifluorooxyhexyl 2- ((tert-butoxycarbonyl) amino) -3-phenyl isovalerate ((2S) -4-azido-6,6,6-trifluorohexyl 2- ((tert-butoxycarbonyl) amino) -3-phenylpropro-panoate) was prepared, having the following structural formula:
Figure RE-GDA0003048558010000252
colorless oil (43.8mg, 49% yield), R f ＝0.4(PE:EA＝5:1)，dr＝1:1。 1 H NMR(400 MHz,CDCl 3 )δ7.30–7.14(m,3H),7.10–7.04(m,2H),4.92(d,J＝8.3Hz,1H),4.51–4.45(m, 1H),4.15–3.94(m,2H),3.66–3.44(m,1H),2.99(d,J＝6.4Hz,2H),2.32–2.07(m,2H),1.82– 1.55(m,2H),1.50–1.40(m,2H),1.35(s,9H)； 13 C NMR(100MHz,CDCl 3 )δ172.1,155.1, 136.04/136.01,129.3,128.6,127.1,125.6(q,J＝277.0Hz),80.0,64.32/64.28,56.4(q,J＝3.4Hz), 54.6,125.6(q,J＝28.5Hz),38.53/38.46,31.2/31.1,28.3； 19 F NMR(376MHz,CDCl 3 )δ–64.05(t, J＝10.4Hz)；HRMS(ESI + )calc’d for C 20 H 27 F 3 N 4 NaO 4 [M+Na] + :467.1877,found 467.1874.
Example 48
In this example, (2S) -1- (4-azido-6,6, 6-trifluorooxyhexyl) 4-cyclohexyl 2- ((tert-butoxycarbonyl) amino) succinic acid ((2S) -1- (4-azido-6,6,6-trifluorohexyl)4-cyclohexyl 2- ((tert-butyloxycaronyl) amino) succinate) was prepared, having the following structural formula:
Figure RE-GDA0003048558010000261
colorless oil (62.7mg, 63% yield), R f ＝0.5(PE:EA＝5:1)，dr＝1:1。 1 H NMR(400 MHz,CDCl 3 )δ5.40(d,J＝8.8Hz,1H),4.78–4.61(m,1H),4.52–4.41(m,1H),4.20–4.02(m, 2H),3.66–3.53(m,1H),2.93–2.87(m,1H),2.75–2.70(m,1H),2.27–2.18(m,2H),1.96–1.55 (m,8H),1.52–1.42(m,1H),1.40–0.92(m,14H)； 13 C NMR(100MHz,CDCl 3 )δ171.2,170.4, 155.4,125.6(q,J＝277.5Hz),80.1,73.7,64.7/64.6,56.4(q,J＝2.8Hz),50.1,38.6(q,J＝28.2Hz), 37.1,31.5,31.1,28.3,25.2,24.9/24.8,23.6； 19 F NMR(376MHz,CDCl 3 )δ–64.09(t,J＝10.5Hz)； HRMS(ESI + )calc’d for C 21 H 33 F 3 N 4 NaO 6 [M+Na] + :517.2244,found 517.2241.
Example 49
In this example, n-hexyl (4R) -4-azido-6,6, 6-trifluorocholate ((4R) -4-azido-6,6,6-trifluorohexyl 4- ((5S,8R,9S,10S,13R,14S,17S) -10,13-dimethyl-3,7, 12-trioxahexadecahydro-1H-cyclopenta [ a ] phenantrene-17-yl) tanoate) was prepared, having the following structural formula:
Figure RE-GDA0003048558010000262
yellow oil (86.7mg, 73% yield), R f ＝0.3(PE:EA＝1:1)，dr＝1:1。 1 H NMR(400MHz, CDCl 3 )δ4.09–3.98(m,2H),3.61–3.58(m,1H),2.91–2.68(m,3H),2.41–1.88(m,19H),1.83 –1.48(m,6H),1.33(s,3H),1.29–1.16(m,4H),1.00(s,3H),0.78(d,J＝6.5Hz,3H)； 13 C NMR (100MHz,CDCl 3 )δ212.0,209.1,208.8,174.0,125.6(q,J＝277.1Hz),63.4,56.9,56.4(q,J＝3.0 Hz),51.8,49.0,46.8/45.6,45.5/45.0,42.8,38.6,38.6(q,J＝28.4Hz),36.5,36.0,35.5/35.3,31.4, 30.4,27.6,25.1/25.0,21.9,18.6,11.8； 19 F NMR(376MHz,CDCl 3 )δ–64.01(t,J＝10.4Hz)；HRMS (ESI + )calc’d for C 30 H 42 F 3 N 3 NaO 5 [M+Na] + :604.2969,found 604.2971.
Example 50
In this example, (3aR,5R,6S,6aR) -5- ((S) -2,2-dimethyl-1, 3-dioxo-4-yl) -2, 2-dimethyltetrahydrofuran [2,3-d ] [1,3] dioxo-6-yl 4-azido-6,6, 6-trifluorooxohexanoate, ((3aR,5R,6S,6aR) -5- ((S) -2,2-dimethyl-1, 3-diolan-4-yl) -2, 2-dimethyltetrahydrofuro [2,3-d ] [1,3] dioxol-6-yl 4-azido-6,6, 6-trifluorohexoxanoate) was prepared having the following structural formula:
Figure RE-GDA0003048558010000271
colorless oily liquid (39.5mg, 44% yield), R f ＝0.4(PE:EA＝5:1)，dr＝1:1。 1 H NMR(400MHz, CDCl 3 )δ5.81(d,J＝3.7Hz,1H),5.31–5.17(m,1H),4.42(s,1H),4.13(s,2H),4.07–3.92(m, 2H),3.77–3.62(m,1H),2.55–2.39(m,2H),2.38–2.18(m,2H),2.02–1.89(m,1H),1.82–1.67 (m,1H),1.45(s,3H),1.34(s,3H),1.24(s,6H)； 13 C NMR(100MHz,CDCl 3 )δ171.0,125.5(q,J＝ 277.2Hz),112.4,109.50/109.48,105.09/105.08,83.4,79.81/79.78,76.43/76.36,72.5/72.4,67.4, 55.9–55.8(m),38.7(q,J＝28.5Hz),30.2/30.1,29.8/29.7,26.94/26.90,26.7,26.2,25.19/25.17； 19 F NMR(376MHz,CDCl 3 )δ–63.98(t,J＝10.4Hz)；HRMS(ESI + )calc’d for C 18 H 26 F 3 N 3 NaO 7 [M+Na] + :476.1615,found 476.1611.
Example 51
In this example, diethyl 2-ethyl-2- (4-azido-6,6,7,7,8,8,9,9,10, 10-fluoroalkyl) -2-methylmalonate (diethyl 2- (4-azido-6,6,7,7,8,8,9,9,10,10,10-undecafluorodecyl) -2-methylmalonate) was prepared, having the following structural formula:
Figure RE-GDA0003048558010000281
colorless oily liquid (65.5mg, 65% yield), R f ＝0.4(PE:EA＝15:1)。 1 H NMR(400MHz,CDCl 3 ) δ4.12(q,J＝7.1Hz,2H),3.75–3.63(m,1H),2.36–2.01(m,2H),1.93–1.71(m,2H),1.62–1.50 (m,2H),1.45–1.27(s,5H),1.18(t,J＝7.1Hz,6H)； 13 C NMR(101MHz,CDCl 3 )δ172.1,172.2, 127.38–99.69(m),61.3,55.6,53.5,35.6,35.51(t,J＝21.3Hz),35.00,20.6,19.9,14.0； 19 F NMR (376MHz,CDCl 3 )δ–81.07(t,J＝9.8Hz),–(113.34–133.62)(m),–(124.42–124.50)(m),– 125.93(t,J＝13.0Hz)；HRMS(ESI + )calc’d for C 17 H 23 F 9 N 3 O 4 [M+H] + :504.1539,found 504.1524.
Example 52
In this example, diethyl 2-ethyl 2- (4-azido-5-n-perfluorodecyl) -2-methylmalonate was prepared with the following formula:
Figure RE-GDA0003048558010000282
colorless oily liquid, R f ＝0.4(PE:EA＝15:1)。 1 H NMR(400MHz,CDCl 3 )δ4.16(q,J＝7.1Hz, 2H),3.80–3.61(m,1H),2.31–2.00(m,2H),1.91–1.75(m,2H),1.61–1.52(m,2H),1.49–1.23 (m,5H),1.15(t,J＝7.1Hz,6H)；HRMS(ESI + )calc’d for C 23 H 23 F 21 N 3 O 4 [M+H] + :804.1375found 804.1389.
Example 53
In this example, diethyl 2-ethyl-2- (4-azido-5-n-pentafluoroethane) -2-methylmalonate was prepared having the following structural formula:
Figure RE-GDA0003048558010000283
colorless oily liquid, R f ＝0.4(PE:EA＝15:1)。 1 H NMR(400MHz,CDCl 3 )δ4.14(q,J＝7.1Hz, 2H),3.78–3.65(m,1H),2.39–2.06(m,2H),1.98–1.77(m,2H),1.69–1.52(m,2H),1.48–1.29 (m,5H),1.14(t,J＝7.1Hz,6H)；HRMS(ESI + )calc’d for C 15 H 23 F 5 N 3 O 4 [M+H] + :404.1530,found 404.1524.
The applicants state that the present invention is illustrated by the above examples to describe the detailed methods and specific products of the present invention, but the present invention is not limited to the above detailed methods and specific products, i.e. it is not meant that the present invention must rely on the above detailed methods to be practiced and limited to the products reported. It should be understood by those skilled in the art that any modification of the present invention, equivalent substitutions of raw materials and additions of auxiliary components, selection of specific modes, etc., of the product of the present invention, and modification of the product skeleton based on the information reported in the present invention, fall within the protection scope and disclosure of the present invention.
The embodiments of the present invention will be described by way of illustration, but are not limited to the description of the present invention, and may be modified within the scope of the present invention or the equivalent added in the claims.

Claims (9)

1. A synthetic method of an ortho perfluoroalkyl substituted azide compound comprises the following steps:
radical initiator, N 3 SO 2 C n F 2n+1 Adding the ortho perfluoroalkyl group substituted azide compound II and olefin I into a solvent, stirring, separating and purifying after reaction to obtain the ortho perfluoroalkyl group substituted azide compound II
Figure FDA0003745344310000011
Wherein the free radical initiator is a peroxy compound or azo free radical initiator;
said N is 3 SO 2 C n F 2n+1 Wherein n is any integer between 1 and 10;
the structure of the olefin I is
Figure FDA0003745344310000012
Wherein R is 1 、R 2 、R 3 、R 4 Are respectively independent and are optionally selected from hydrogen, C1-C18 alkyl, C1-C18 alkyl substituted by C6-C18 aryl, C1-C12 alkyl substituted by heteroatom N, O, S or C1-C12 alkyl substituted by halogen F, Cl, Br and I.
2. The method of claim 1, wherein: the structure of the peroxide compound free radical initiator is
Figure FDA0003745344310000013
Wherein R is 5 、R 6 Independently selected from C1-C18 alkyl, C6-C18 aryl substituted ester group, C1-C18 alkyl substituted ester group or hydrogen; the azo free radical initiator has the structure
Figure FDA0003745344310000014
Wherein R is 7 、R 8 Independently selected from C1-C18 alkyl or cyano-substituted C1-C18 alkyl.
3. The method of claim 1, wherein: the free radical initiator is selected from dilauryl peroxide BPO, dilauryl peroxide LPO, tert-butyl peroxybenzoate, di-tert-butyl peroxide DTBP, tert-butyl hydroperoxide TBHP, 2,6, 6-tetramethylpiperidine oxide TEMPO, azobisisobutyronitrile AIBN, pentafluorobenzoyl peroxide, 4-trifluoromethyl benzoyl peroxide or 4-methyl benzoyl peroxide.
4. The method of claim 1, wherein: said N is 3 SO 2 C n F 2n+1 Wherein n is 1,2, 4, 10.
5. The method of claim 1, wherein: the solvent is selected from one or a mixture of more of acetonitrile, chlorobenzene, dichloroethane, chloroform, dimethyl sulfoxide, ethyl acetate, acetone, ethylene glycol dimethyl ether, n-pentane, cyclohexane, n-hexane, dimethylformamide, methyl tert-butyl ether, cyclopentyl methyl ether, benzonitrile and 1, 4-dioxane.
6. The method of claim 1, wherein: the olefin I, N 3 SO 2 C n F 2n+1 And the molar ratio of the free radical initiator is 1:1.0-5.0: 0.05-5.
7. The method of claim 1, wherein: the reaction temperature is 20-100 ℃, and the reaction time is 0.1-24 hours.
8. The method of claim 1, wherein: the separation and purification method comprises column chromatography, thin layer chromatography, recrystallization or reduced pressure distillation.
9. The method as claimed in claim 8, wherein the eluent used in the column chromatography is a mixture of petroleum ether and ethyl acetate, wherein the volume ratio of petroleum ether to ethyl acetate is 2-100: 1.
CN202011508287.0A 2020-12-18 2020-12-18 Synthesis method of ortho-perfluoroalkyl substituted azide compound Active CN113277959B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202011508287.0A CN113277959B (en) 2020-12-18 2020-12-18 Synthesis method of ortho-perfluoroalkyl substituted azide compound

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202011508287.0A CN113277959B (en) 2020-12-18 2020-12-18 Synthesis method of ortho-perfluoroalkyl substituted azide compound

Publications (2)

Publication Number Publication Date
CN113277959A CN113277959A (en) 2021-08-20
CN113277959B true CN113277959B (en) 2022-08-30

Family

ID=77275400

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202011508287.0A Active CN113277959B (en) 2020-12-18 2020-12-18 Synthesis method of ortho-perfluoroalkyl substituted azide compound

Country Status (1)

Country Link
CN (1) CN113277959B (en)

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008122030A2 (en) * 2007-04-02 2008-10-09 University Of South Alabama Carbon dioxide scrubbing using ionic materials
CN107840796B (en) * 2017-11-10 2020-12-15 西安近代化学研究所 Preparation method of trifluoromethyl alkenyl ester

Also Published As

Publication number Publication date
CN113277959A (en) 2021-08-20

Similar Documents

Publication Publication Date Title
Martin et al. Aspects of the intramolecular Diels-Alder reactions of some 1, 3, 9-trienic amides, amines, and esters. An approach to the pentacyclic skeleton of the yohimboid alkaloids
CN109293468B (en) Method for synthesizing cis-olefin through decarboxylation coupling reaction of NHP ester and terminal aryl alkyne under catalysis of iridium
Shirokane et al. Total syntheses of (±)-Gephyrotoxin and (±)-Perhydrogephyrotoxin
Lin et al. DABCO-catalyzed ring opening of activated cyclopropanes and recyclization leading to γ-lactams with an all-carbon quaternary center
Cran et al. The intramolecular Morita–Baylis–Hillman-type alkylation reaction
CN113277959B (en) Synthesis method of ortho-perfluoroalkyl substituted azide compound
CN113620918A (en) Method for synthesizing spiro compound through Lewis acid catalyzed [3+2] cycloaddition reaction
EP3464297B1 (en) Process for preparation of eribulin and intermediates thereof
Yang et al. Lewis acid-catalyzed atom transfer radical cyclization of unsaturated β-keto amides
WO2021045879A1 (en) Synthesis of deuterated aldehydes
Rui et al. Rh (i)-Catalyzed stereoselective intramolecular cycloaddition reactions of ene-vinylidenecyclopropanes for the construction of fused 6, 5-bicyclic skeletons with a quaternary all-carbon stereocenter
Li et al. PhI (OAc) 2-mediated additions of 2, 4-dinitrophenylsulfenamide with methylenecyclopropanes (MCPs) and a methylenecyclobutane (MCB)
CN109081800B (en) Containing CF3Synthesis method of indoline and 1,2,3,4-tetrahydroisoquinoline
CN112047908B (en) Preparation method of ferric chloride promoted 2, 3-dihydrofuran derivative
CN113912637A (en) Method for catalytically synthesizing alkyl silicon compound by using organic dye as photocatalyst
US5554764A (en) Preparation of pyrrol and oxazole compounds: formation of C-acyl-α-amino acid esters therefrom
Volochnyuk et al. Synthesis of gem‐Difluorocyclopropanes
CN109134306B (en) Alkyl ketone amide and oxime amide compound thereof, and preparation and application thereof
JP6067700B2 (en) Alcohol oxidation catalyst and alcohol oxidation method using the same
CN113233980B (en) Synthesis method of beta-chloroacid ester and alpha, beta-unsaturated acid ester compound
Šebesta et al. Enantioselective Michael additions of aldehydes to nitroalkenes catalyzed with ionically tagged organocatalyst
CN110294688A (en) A kind of preparation method for the azido compound that γ-position chlorine replaces
CN113336692B (en) 1, 6-diene controllable double cyclization reaction method initiated by sulfonyl free radical
JP7244905B2 (en) Organocatalysts for highly stereoselective asymmetric aldol reactions and their applications
CN108929226B (en) Method for preparing benzoyl formate derivative

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant